Biomedical Engineering Reference
In-Depth Information
tissue level). Even formal and quantitative approaches like system dynamics-
based modeling of particular molecular pathways are descriptive because they
use an established set of rules (e.g., formal reaction kinetics and diffusion) to
describe and predict in detail the time evolution of a
particular instance
of a
class of system whose generic behavior is known given the set of equations and
conditions (see this volume, Part II, chapter 2, by Socolar). While useful to pre-
dict the behavior of a particular system in a "bottom-up" approach once its
component parts are sufficiently characterized, none of these approaches directly
address the challenge of integration by transcending various levels organization
and elucidating the basic rules involved.
In view of the rapid rise of molecular biology and genomics, some biolo-
gists did voice caution about the limitations of this descriptive and reductionist
stance (12,33,37,45,49,55,62,53), essentially calling attention to Aristotle's in-
sight that the "whole is different from the sum of its parts." However, it is only
now, at the threshold of post-genomic and systems biology, that life scientists
are beginning to realize that an accurate description of all the parts that comprise
a living cell is not equal to understanding how it functions (29). Sometimes cap-
turing the impression of the whole picture with a glance can give deeper insights
and yield information not obtained by reproducing it pixel by pixel. Although
biologists have yet to adopt the approach of "coarse-graining" to gain insight
into fundamental, system-wide properties, this method is often used by physi-
cists (25,71). Only by adjusting our focus plane to various levels of organiza-
tion, and "zooming" in and out on the magnification, can we reveal the
fundamental principles that govern what makes the whole (the organism) differ-
ent from the sum of its parts (the molecules).
To do so, biologists must free themselves from their "divide and conquer"
mentality and their adherence to molecular description, be it qualitative or quan-
titative, one at a time or in massively parallel fashion, as the only mode of ex-
planation. Instead, they must join physicists in their willingness to embrace
abstraction and generalization. Conceptual and formal tools are also needed that
go beyond descriptive mathematical modeling of particular molecular pathways.
In fact, at the same time that the molecular biologist now faces this new chal-
lenge, the science of "complex systems" appears to have matured into a disci-
pline in its own right. Even if a rigorous scientific underpinning remains to be
established (if it is possible at all), it has encouraged scientists from various
fields, such as physics, biology, engineering, business, and the social sciences,
to join forces and to a take more formal and general approach to understand
principles of complex systems rather than simply creating models that only re-
enact them in silico with all the details.
A specific formalism that is particularly useful here is based on the idea that
a complex system can be treated as a
network
of interacting parts in a most gen-
eral sense. A network can be a physical or mechanical structure, as well as an
abstract representation of how information flows between interacting elements
